During the past decade growth hormone-releasing factors (GRF) of human pancreatic islet tumor origin (hpGRF) have been isolated, characterized and shown to possess growth hormone (GH)-releasing activity in rat anterior pituitary in vitro and in vivo by (1) R. Guillemin, P. Grazeau, P. Bohlen, F. Esch, N. Ling, and W. B. Wehrenberg [Science, 218, 585 (1982)]and (2) J. Spiess, J. Rivier, M. Thorner, and W. Vale [Biochemistry, 21, 6037 (1982)]. A synthetic hp GRF(1-29)-NH.sub.2, an amidated fragment of the natural hp GRF, has also been prepared and reported to possess full intrinsic biological activity by Spiess et al. of reference (2).
Additionally, it has been found that an increase in growth hormone (GH)-release in animals can be attained by substituting D-amino acids for L-amino acids of natural hpGRF, especially in the 2 and 3 positions, (Lance et al., Biochemical and Biophysical Research Communications. Vol. 119, No. 1, 1984, pp 265-272: Vale, Jr. et al., U.S. Pat. No. 4,528,190). Likewise, Vale, Jr. et al., have disclosed in the above-mentioned patent that an increase in GH-release is obtained by inserting an N .sup..alpha. -methyl (or C .sup..alpha. -methyl-substituted amino acid in positions 1 and 2 of hpGRF. These investigators, however, neither extended the length of the alkyl group beyond methyl on the N-terminus of the hpGRF peptides, nor suggested that such extension would enhance the activity of the hpGRF peptides.